The emphasis of this research proposal is to analyze cellular environments which may influence regeneration in the adult mammalian central nervous system (CNS). Embryonic neural tissue implanted into the mature CNS will be utilized as an experimental model system in which the presynaptic or postsynaptic cellular environments can be manipulated in an attempt to enhance regeneration in specific neurons of the septal-hippocampal complex. For most experiments embryonic septum or hippocampus will be placed adjacent to specific lesioned axons from the entorhinal cortex, septum, and hippocampus. Four experimental situations will be analyzed: 1) the influence of the appropriate embryonic target tissue on retrograde neuronal reactions and regenerative abilities of neurons in the adult host; 2) the specificity of the regenerative response for the appropriate postsynaptic target, 3) the effect of reintroduction of the appropriate lesioned afferent on the cellular reorganization occurring at the postsynaptic target site, and 4) the glial response along the transition zone between the embryonic implant and the mature host CNS. The direction of axonal growth, the location of terminal projections, and the cells of origin of the projections which result from interactions between the embryonic and adult neurons will be analyzed with light imcroscopic, electron microscopic, and biochemical assay procedures. This will be accomplished by employing light microscopic anterograde and retrograde neuroanatomical tracing techniques such as acetylcholinesterase staining, monoamine histochemical fluorescence, neurofibrillar degeneration methods, the autoradiographic procedure, the horseradish peroxidase and retrograde fluorescent tracing methods, and immunocytochemical staining techniques. Biochemical assays will measure glutamate uptake and choline acetyltransferase activity. The results of the proposed experiments should provide information which will be applicable for understanding the cellular responses which are necessary in order to promote regeneration in the adult human CNS following traumatic brain and spinal cord injuries.